This research will explore the mechanisms by which the immune system initiates and modulates inflammatory processes. Methods for the quantification of cellular chemotaxis in vitro have been developed for the study of granulocytes, macrophages, lymphocytes and fibroblasts. We have recently demonstrated by direct binding studies, the presence of specific receptors for chemotactic peptides on human granulocytes. We will now further characterize these receptors and determine if human inflammatory or immune deficiency diseases are associated with abnormalities of chemotactic factor receptor function. We developed methodology to study human fibroblast chemotaxis and showed that stimulated human lymphocytes produce a lymphokine which is chemotactic for fibroblasts. We will now determine the role of complement and other serum factors in mediating the accumulation of fibroblasts locally. We also developed methodology to quantify human lymphocyte chemotaxis and during the upcoming year will explore the cellular and humoral mediators of lymphocyte accumulation as well as the physiology of lymphocyte locomotion. The role of inflammatory cell accumulation in protecting the host against endotoxin lethality will be studied using mice resistant to endotoxin (C3H/Hej) as well as normally susceptible mice. In sum, this research will elucidate mechanisms of inflammatory cell accumulation at sites of immunological reactions and characterize the factors which initiate and modulate the intensity and effectiveness of inflammatory responses in eliminating antigens. BIBLIOGRAPHIC REFERENCES: Snyderman, R., Seigler, H., Meadows, L. Abnormalities of Monocyte Chemotaxis in Patients with Malignant Melanoma and Effects of Immunotherapy and Tumor Removal. J. Nat. Cancer Inst. 58:37-41, 1977. Allen, E.D., Snyderman, R., Meadows, L., and Pinnell, S.R. Generalized Microsporum Audouinii Infection and Depressed Cellular Immunity Associated with a Missing Plasma Factor Required for Lymphocyte Blastogenesis. Amer. J. Med. 1977 (In press).